The incidence of pregnancy-associated gingivitis reportedly ranges from near 60% in normal women to 96% in diabetic women. Despite such statistics, treatment options are limited because the pathogenesis of this condition is so poorly understood. Since gingivitis is similarly seen during puberty and after menopause, an imbalance or hypersecretion of estrogen and/or progesterone has been regarded as a likely cause for such localized inflammation. Steroid hormones are reported to bind to oral tissues and to stimulate a number of steroid-metabolizing enzymes. However, very little hormone-related data have been generated in single cell types; most work was done in biopsy samples or homogenates of these. Thus such information represents the summation of steroidal metabolism by several cell types, including bacteria. The infiltration of leukocytes into the gingiva clearly represents the response of the immune system to the challenge of plaque-associated bacteria. It is becoming evident that the immune system is affected by the endocrine status of the individual, and during pregnancy a number of immune responses are depressed. This proposal will test the hypothesis that one (or more) of the hormones whose levels increase during pregnancy modulates the local response of the resident gingival cells to the cytokines produced in defense against invading bacteria. Cultured gingival fibroblasts will be treated with estrogen, progesterone, testosterone, and/or prolactin, then exposed to interleukin-1 or tumor necrosis factor-alpha, which are produced by leukocytes stimulated by bacterial lipopolysaccharide. The secretion of interleukin-6, a pleiotropic cytokine with multiple biological effects, and the release of prostaglandin E(2), a mediator of osteoclastic bone resorption,will be measured as indicators of the gingival fibroblasts' responsiveness to inflammatory stimuli. In a pilot study, interleukin-6 will be extracted from gingival crevicular fluid from pregnant and non- pregnant women, and measured by an ELISA. Future work will be directed toward identification of the site and mechanism of action of the hormonal modulation which may be observed. The growing recognition of womens' health concerns emphasizes the timeliness of this proposal.